Pollen-Derived E1-Phytoprostanes Signal via PPAR-γ and NF-κB-Dependent Mechanisms
Pollen-Derived E1-Phytoprostanes Signal via PPAR-γ and NF-κB-Dependent Mechanisms
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DOI：
10.4049/jimmunol.0802613
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发表时间：
2009-06-01
影响因子：
4.4
通讯作者：
Traidl-Hoffmann, Claudia
中科院分区：
文献类型：
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作者：
Gilles, Stefanie;Mariani, Valentina;Traidl-Hoffmann, Claudia
在潮湿的环境中，如粘膜表面，花粉粒不仅释放过敏原，而且释放促炎和免疫调节脂质，称为花粉相关脂质介质。其中，E-1-植物前列腺素（PPE 1）被鉴定为调节树突状细胞（DC）功能：PPE 1抑制DC产生IL-12的能力并增强DC介导的幼稚T细胞的T（H）2极化。PPE 1作用于DC的机制仍不清楚。因此，我们分析了候选信号元件及其在PPE 1介导的DC功能调节中的作用。桦树花粉水提取物诱导了一个显着的cAMP反应在DC中，可以部分阻断EP 2和EP 4拮抗剂。相反，PPE 1几乎不诱导cAMP，并且对IL-12产生的抑制作用大多不依赖于EP 2和EP 4。相反，PPE 1通过涉及核受体PPAR-gamma的机制抑制LPS诱导的IL-12 p70的产生。最后，PPE 1通过抑制I κ B-α降解、p65向细胞核的易位以及与其靶DNA元件的结合，有效地阻断DC中的NF-κ B信号传导。我们的结论是，花粉衍生的PPE 1通过PPAR-γ依赖性途径调节DC功能，导致NF κ B B活化的抑制，并导致DC IL-12产生减少和连续的T（H）2极化。免疫学杂志，2009，182：6653-6658.
In a humid milieu such as mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E-1-phytoprostanes (PPE1) were identified to modulate dendritic cell (DC) function: PPE1 inhibit the DC's capacity to produce IL-12 and enhance DC mediated T(H)2 polarization of naive T cells. The mechanism(s) by which PPE1 act on DC remained elusive. We thus analyzed candidate signaling elements and their role in PPE1-mediated regulation of DC function. Aqueous birch pollen extracts induced a marked cAMP response in DC that could be blocked partially by EP2 and EP4 antagonists. In contrast, PPE1 hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE1 inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-gamma. Finally, PPE1 efficiently blocked NF-kappa B signaling in DCs by inhibiting I kappa B-alpha degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE1 modulate DC function via PPAR-gamma dependent pathways that lead to inhibition of NF kappa B activation and result in reduced DC IL-12 production and consecutive T(H)2 polarization. The Journal of Immunology, 2009, 182: 6653-6658.